Role of Advanced Screening Technologies for Early Detection of Breast Cancer Project Summary/Abstract This application addresses broad Challenge Area (05): Comparative Effectiveness Research and specific Challenge Topic, 05-CA-105 CISNET (The Cancer Intervention and Surveillance Modeling Network). The goals of this research are targeted at evaluating the benefits associated with advanced screening technologies for breast cancer screening. It is planned to apply the stochastic model developed by Lee and Zelen (2008) to address the effectiveness of advanced screening technologies in the early detection of breast cancer. The Lee-Zelen model (2008) has been developed as part of the CISNET breast group. The model predicts breast cancer mortality as a function of the disease natural history and detection process. The principal assumptions of the model are that: i) breast cancer is a progressive disease and ii) mortality benefit from screening is due to a stage shift in diagnosis. Among the rapidly emerging advanced screening technologies, digital mammography (DM) and magnetic resonance imaging (MRI) have been reported to be more sensitive in diagnosing breast cancer. However the mortality benefit associated with these screening modalities has not been evaluated. This grant will focus on evaluating the mortality benefit from DM and MRI screening. The digital mammographic imaging screening trial showed that DM was significantly more sensitive than film mammography in screening women under age 50 or women of any age with very dense breasts (Pisano et al., 2005). MRI has been shown to be more sensitive than mammography in detecting breast cancer in women with inherited susceptibility to breast cancer (Kreige et al., 2004;Leach et al., 2005). An important issue which will be investigated deals with optimal screening strategies using DM and MRI. A screening program is characterized by: i) the age to begin a screening program, ii) the times between examinations and 3) possibly the age to end screening. There are so many potential permutations of these variables that clinical trials cannot possibly examine all of the possible permutations. Furthermore randomized trials are not feasible. The only way to investigate the problem is to have an analytical model of the screening process which incorporates the main features of the disease and the screening process. The potential savings of having screening programs based on risk are enormous. Specifically it is planned to: Estimate the mortality benefit of DM in women under age 50 and women of any age with dense breasts. Estimate the potential mortality benefit of DM if disseminated in the U.S. population. Estimate the mortality benefit of MRI in women with elevated risk of developing breast cancer. Find optimal screening exam schedules which depend on breast density. Investigate optimal screening strategies by risk status for DM and MRI screening modalities. Role of Advanced Screening Technologies for Early Detection of Breast Cancer PUBLIC HEALTH RELEVANCE: Magnetic resonance imaging (MRI) may be utilized for breast cancer screening in high risk populations and digital mammography may be advantageous for screening women with dense breasts. This project will use the Lee-Zelen's (2008) mathematical model to evaluate mortality benefit as well as to find optimal screening strategies for these advanced screening modalities. As it is difficult to investigate these problems using randomized clinical trials, mathematical models can make a significant contribution in understanding the potential gain from these screening modalities.